THE JOURNAL · INTERACTIVE
How psilocybin works.
From the molecule to the brain in six steps: what psilocybin is, what the body turns it into, the receptor it acts on, what brain imaging reports, how long effects last in controlled studies, and what is still unknown. Every fact links to its source.
Educational only, not medical or legal advice. Evidence levels are marked in each step: most human studies here are small, and the brain-network ideas are findings and hypotheses, not settled fact. Checked 2026-10-25.
Step by step.
STEP 1 OF 6
Psilocybin, the molecule
Psilocybin is a tryptamine. Its core is an indole: a six-membered carbon ring fused to a five-membered ring that holds a nitrogen. A two-carbon side chain runs off that core and ends in a nitrogen carrying two methyl groups.
What sets psilocybin apart is at position 4 of the ring: a phosphate group, one phosphorus atom bound to four oxygens. PubChem lists its formula as C12H17N2O4P.
Evidence Established chemistry. The drawing uses PubChem's 2D coordinates; hydrogen atoms are left out.
Sources PubChem: psilocybin
STEP 2 OF 6
In the body: psilocybin becomes psilocin
Psilocybin is mainly a prodrug. The enzyme alkaline phosphatase removes the phosphate group, leaving psilocin (C12H16N2O), which has a hydroxyl group (OH) where the phosphate was.
The switch is fast. A systematic review of 14 studies calls the dephosphorylation rapid, and one study of 12 healthy adults found no psilocybin in blood or urine at all, only psilocin and its breakdown products.
Psilocin is broken down in turn, mainly by the liver enzymes CYP2D6 and CYP3A4 with a smaller role for monoamine oxidase A. Psilocin-O-glucuronide is the main form found in urine.
Evidence Human pharmacokinetic studies, mostly small (6 to 28 people per study), plus reviews.
Sources Dinis-Oliveira 2017, Meshkat 2025, Brown 2017, PubChem: psilocin
STEP 3 OF 6
The receptor: psilocin at serotonin 2A
Psilocin looks a lot like serotonin, the body's own messenger. Both have the same indole core and a two-carbon chain ending in a nitrogen. The differences are small: psilocin's hydroxyl sits at position 4 instead of 5, and its nitrogen carries two methyl groups where serotonin's has two hydrogens.
Psilocin acts as an agonist or partial agonist at the serotonin 2A (5-HT2A) receptor, a protein in the membrane of nerve cells. In a PET imaging study of 8 healthy volunteers, how many 5-HT2A receptors were occupied, and how much psilocin was in the blood, both tracked how intense people rated the experience.
Blocking the receptor points the same way. In placebo-controlled studies in healthy volunteers, ketanserin, a drug that blocks 5-HT2A receptors, blocked or weakened psilocybin's effects. Psilocin also acts at other receptors, such as 5-HT1A, so the lock-and-key picture is a simplification.
Evidence Human PET and blocker studies with small samples (8 to 16 people), consistent with earlier animal work.
Sources PubChem: serotonin, PubChem: psilocin, Dinis-Oliveira 2017, Madsen 2019, Vollenweider 1998, Quednow 2012
STEP 4 OF 6
Brain networks: findings and debates
Finding: in an fMRI study of two groups of 15 healthy volunteers, psilocybin brought only decreases in blood flow and brain signal, largest in hub regions, and weaker coupling between the medial prefrontal and posterior cingulate cortex. The weaker the prefrontal activity, the stronger people rated the effects.
Finding: a 2024 study scanned 6 healthy adults about 18 times each. Psilocybin changed functional connectivity more than three times as much as a stimulant used for comparison. Regions within a network fell out of step and the boundaries between networks blurred. The effect was strongest in the default mode network (DMN), which the authors describe as thought to shape our sense of space, time and self, and a drop in connectivity between the hippocampus and the DMN lasted for weeks.
Debate: the "entropic brain" hypothesis proposes that psychedelic states show more varied, less predictable brain activity, and a later model (REBUS) proposes that they loosen the hold of high-level beliefs. Its author argues the evidence has grown; a 2026 critical review counters that entropy changes are not specific to psychedelics and that different entropy measures disagree.
Caution: a 2022 review by many of the field's own researchers counted 42 papers drawn from only 17 studies, with two datasets behind more than half of them and analysis methods that vary from paper to paper.
Evidence Human imaging with small samples; entropy and REBUS are hypotheses, not settled fact. The graph is stylised, not real data.
Sources Carhart-Harris 2012, Siegel 2024, Carhart-Harris 2014, Carhart-Harris & Friston 2019, Carhart-Harris 2026, Moses 2026, McCulloch 2022
STEP 5 OF 6
Time course: what controlled studies report
Health Canada says the effects of magic mushrooms appear within 15 to 45 minutes and usually last four to six hours.
Controlled studies in healthy volunteers give closer figures. In a crossover study of 28 people taking capsules in a laboratory, modelled effects began after about 0.8 hours on average, peaked after 2.1 to 2.3 hours and ended after 6.4 to 7.3 hours. Individual people ranged widely: onset from 0.1 to 1.8 hours, offset from 3.7 to 12 hours.
Blood levels follow a similar arc. Psilocin peaked about 2 hours after oral psilocybin in a larger study, and across studies the time to peak ranged from 1.8 to 4 hours, with a half-life of 1.5 to 4 hours.
Evidence Averages from controlled laboratory settings. Individuals vary widely, and these figures are not a guide to any person's experience.
Sources Health Canada, Holze 2022, Holze 2023, Hasler 1997, Meshkat 2025
STEP 6 OF 6
What we don't know
How receptor activity turns into experience. The links between 5-HT2A occupancy, network changes and what people report are correlations from small groups, not a worked-out mechanism.
Whether "entropy" is the right measure. Supporters and critics read the same imaging literature differently, and different entropy measures do not always agree.
How well the imaging findings replicate. Much of the literature rests on a few datasets analysed in different ways.
What lasting changes mean. A connectivity change that lasted weeks was seen in 6 people, and the neuroplasticity it is often linked to has been shown in animal models. What either means for health is not established.
Why people differ so much. Timing and blood levels vary widely between individuals, and kinetics differ by route and species.
Health Canada says there are no approved therapeutic products containing psilocybin, in Canada or elsewhere.
Evidence Open questions, each drawn from the reviews and studies cited in the earlier steps.
Sources Madsen 2019, Siegel 2024, Moses 2026, Carhart-Harris 2026, McCulloch 2022, Meshkat 2025, Health Canada
The short version.
- The molecule. Psilocybin is a tryptamine with a phosphate group at position 4 of its indole ring.
- In the body. In the body, alkaline phosphatase removes that phosphate quickly, leaving psilocin, the active form.
- The receptor. Psilocin resembles serotonin and acts at serotonin 2A receptors; blocking those receptors blocked or weakened the effects in human studies.
- Brain networks. Imaging studies in small groups report less synchronised, less separated brain networks, especially the default mode network. Theories such as the entropic brain remain debated.
- Time course. Controlled studies report onset within about an hour on average, a peak around two hours and an end around six to seven hours, with wide differences between people.
- Unknowns. How receptor activity becomes experience, how well the imaging findings replicate and what lasting changes mean are still open questions.
Health Canada’s position.
Health Canada’s page on magic mushrooms (updated 20 October 2026) says that producing, selling and possessing magic mushrooms is illegal in Canada, and that there are no approved therapeutic products containing psilocybin in Canada or elsewhere. It describes three routes through which a regulated health care practitioner may seek legal access for a patient: clinical trials, which it calls the most appropriate route, the Special Access Program, and individual exemptions under subsection 56(1) of the Controlled Drugs and Substances Act. This is a summary of the government’s page, not legal advice. For current studies, see the clinical trials tracker; for the law, the law tracker.
How we built this.
- Molecules are drawn in code from PubChem’s 2D coordinates, with hydrogens left out. The receptor “lock” and the network graph are stylised drawings, not structures or data.
- Studies were read on Europe PMC: abstracts for all, and the open full text where we quote a table or a sample size. Times come from controlled studies in healthy volunteers; doses are left out on purpose.
- Evidence levels are given in each step. Most human imaging and receptor studies here enrolled between 6 and 30 people.
Keep reading.
- Psilocin vs psilocybin: what is the difference?
- What is psilocybin?
- Does psilocybin rewire the brain?
- Psilocybin studies library: the major studies in plain English
- Psilocybin timeline: history, science and law
- Test yourself: the magic mushroom quiz
- Magic mushroom glossary
- Safety guide and Toronto help lines
SOURCES
- Psilocybin (CID 10624). PubChem, U.S. National Library of Medicine Used for: Formula C12H17N2O4P, IUPAC name and the 2D atom coordinates drawn in steps 1 and 2.
- Psilocin (CID 4980). PubChem, U.S. National Library of Medicine Used for: Formula C12H16N2O and IUPAC name (a 4-hydroxy indole with a dimethylaminoethyl side chain).
- Serotonin (CID 5202). PubChem, U.S. National Library of Medicine Used for: Formula C10H12N2O, IUPAC name (a 5-hydroxy indole with an aminoethyl side chain) and the 2D coordinates drawn in step 3.
- Magic mushrooms. Health Canada, canada.ca (page modified 2026-10-20) Used for: Onset and duration in general terms; legal status; the three access pathways; no approved therapeutic psilocybin products.
- Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Dinis-Oliveira RJ. Drug Metabolism Reviews 49(1):84–91, 2017. Review; abstract read. Used for: Psilocybin as a prodrug dephosphorylated by alkaline phosphatase; both compounds as 5-HT2A agonists or partial agonists; psilocin-O-glucuronide as the main urinary metabolite.
- Pharmacokinetics of Psilocybin: A Systematic Review. Meshkat S, et al. Pharmaceutics 17(4):411, 2025. Systematic review of 14 studies (8 laboratory, 6 clinical with 112 healthy people); abstract and open full text read. Used for: Rapid dephosphorylation; time to peak blood level 1.8–4 h and half-life 1.5–4 h across studies; CYP2D6, CYP3A4 and MAO-A; variability by dose, route and species.
- Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown RT, et al. Clinical Pharmacokinetics 56(12):1543–1554, 2017. 12 healthy adults; abstract read. Used for: No psilocybin found in plasma or urine, only its metabolite psilocin; psilocin half-life about 3 h.
- Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Hasler F, et al. Pharmaceutica Acta Helvetiae 72(3):175–184, 1997. Two small studies (6 people each); abstract read. Used for: Psilocin peaked in blood about 105 ± 37 minutes after oral psilocybin, and within minutes after intravenous psilocybin, pointing to rapid dephosphorylation.
- Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants. Holze F, et al. Clinical Pharmacology & Therapeutics 113(4):822–831, 2023. Healthy volunteers in three groups of 23–28; abstract read. Used for: Psilocin peaked in blood after about 2 h on average; mean duration of subjective effects 5.5–6.4 h across groups; body weight did not change the kinetics.
- Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Holze F, et al. Neuropsychopharmacology 47(6):1180–1187, 2022. 28 healthy volunteers, crossover; open full text read (Table 1). Used for: Modelled time to onset, maximal effect, offset and effect duration for the two psilocybin conditions, as means and individual ranges.
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Madsen MK, et al. Neuropsychopharmacology 44(7):1328–1334, 2019. PET imaging, 8 healthy volunteers; abstract read. Used for: 5-HT2A receptor occupancy and blood psilocin both tracked the rated intensity of the experience.
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Vollenweider FX, et al. NeuroReport 9(17):3897–3902, 1998. Controlled study in healthy volunteers; abstract read. Used for: Effects blocked by the 5-HT2A antagonist ketanserin, in a dose-dependent way.
- Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers. Quednow BB, et al. Neuropsychopharmacology 37(3):630–640, 2012. Randomised, double-blind, 16 healthy participants; abstract read. Used for: Ketanserin (a 5-HT2A/2C blocker) attenuated psilocybin's effects; notes psilocin also acts at 5-HT1A receptors.
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Carhart-Harris RL, et al. PNAS 109(6):2138–2143, 2012. fMRI, two groups of 15 healthy volunteers, intravenous psilocybin vs placebo; abstract read. Used for: Only decreases in blood flow and BOLD signal, largest in hub regions; reduced coupling between the medial prefrontal and posterior cingulate cortex.
- Psilocybin desynchronizes the human brain. Siegel JS, et al. Nature 632(8023):131–138, 2024. Precision functional mapping, about 18 MRI visits each; 6 densely sampled healthy adults in the main analysis; abstract and open full text read. Used for: Connectivity change more than three times that of a stimulant control; desynchronisation blurred network boundaries, strongest in the default mode network; a drop in hippocampus–DMN connectivity lasted weeks.
- Psychedelic resting-state neuroimaging: A review and perspective on balancing replication and novel analyses. McCulloch DE, et al. Neuroscience & Biobehavioral Reviews 138:104689, 2022. Review; abstract read. Used for: 42 papers from 17 unique studies; methods vary; two datasets behind over half of the papers; ambiguous terms.
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Carhart-Harris RL, et al. Frontiers in Human Neuroscience 8:20, 2014. Theory paper; abstract read. Used for: Proposes that the psychedelic state shows higher entropy in brain activity and a breakdown of organised default mode network activity.
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Carhart-Harris RL, Friston KJ. Pharmacological Reviews 71(3):316–344, 2019. Theory and review; abstract read. Used for: Proposes that psychedelics relax the weight of high-level beliefs (priors), letting bottom-up information count for more.
- The entropic brain today. Carhart-Harris RL. Brain 149(10):3362–3378, 2026. Review by the hypothesis's author; abstract read. Used for: Argues the hypothesis has gathered supportive evidence across many states of consciousness.
- A critical review of brain entropy as a biomarker of the psychedelic state. Moses B, Doss MK, Tagliazucchi E. Neuroscience & Biobehavioral Reviews 186:106720, 2026. Critical review; abstract read. Used for: Entropy changes are not specific to psychedelics; several entropy measures disagree; limited evidence links entropy to the richness of experience.